The C-IV cytoplasmic domain of the human Beta-1 adrenergic receptor (B1-AR) is a novel 10 amino acid alpha-helical structure. It encompasses the residues between 381proline to 390leucine. The organization of C-IV provides a novel architecture for the guanine-nucleotide binding-protein-coupled receptor (GPCR) superfamily that was identified in the crystal structure of the GPCR rhodopsin. Because of their locations within this alpha-helix 384arginine (R384) and 385lysine (L385) are putative candidates for coupling the B1-AR to the guanine-nucleotide binding protein (G-protein) and adenylyl cyclase signal transduction system. The purpose of this study is to characterize the role of the C-IV domain of the B1-AR in signal transduction. Specifically residues R384 and K385 were mutated by site-directed mutagenesis into residues that were not disruptive to the domain's tertiary structure. The involvement of these specific residues will be characterized by receptor agonist-mediated desensitization, sequestration, and down-regulation; radioligand binding; cyclic AMP accumulation/adenylyl cyclase activation; confocal/fluorescence microscopy; and bioluminescence resonance energy transfer assays. This study focuses on an important area of sympathetic innervation which is relevant to hypertension, fluid homeostasis, and renal disease progression. [unreadable] [unreadable]